1. Field of the Invention
This invention relates to a human IgG.sub.1 type monoclonal antibody, a method for the production thereof, and a hybridoma capable of producing the antibody.
The human IgG.sub.1 type monoclonal antibody provided by the present invention is specific to the nicotinic acetylcholine receptor (hereinafter referred to as "AChR" for short). It is useful in the diagnosis of myasthenia gravis which is characterized mainly by impairment of neuromuscular transmission caused by the presence of autoantibodies against the AChR present on the post-synaptic membrane of the neuromuscular junction and is also useful as a raw material for the production of an antiserum or monoclonal antibody against the aforementioned autoantibodies which is expected to be utilized in the treatment of myasthenia gravis.
2. Prior Art Statement
It has been reported in the literature [Proceedings of the National Academy of Sciences of the United States of America, Vol. 77, pages 755-759 (1980)] that a hybridoma was obtained by fusing the spleen cells of rats immunized with an acetylcholine receptor extracted from the electric organ of torpedos or electric eels with the myeloma cell line originating in mice and a rat monoclonal antibody against acetylcholine receptor was obtained by using the hybridoma mentioned above. Production of a human monoclonal antibody against acetyl choline receptor by the use of a transformed cell line obtained by transforming the lymphocytes collected from the thymus of a patient of myasthenia gravis with Epstein-Barr virus has been reported in literature [Science, Vol. 215, pages 995-997 (1982)]. It has been known to the art that a human monoclonal antibody similar to the autoantibody against acetylcholine receptor possessed by a patient of myasthenia gravis is produced by using a hybridoma which is obtained by fusing peripheral mononuclear cells of a patient of myasthenia gravis with human myeloma cell line resistant to 8-azaguanine [Japanese Patent Public Disclosure SHO 59(1984)-231024].
Generally, when a monoclonal antibody originating in such animals as mice and rats is administered to the human body, the human body induces an immune response to the monoclonal antibody and there may ensue elimination of the activity of the monoclonal antibody and side effects such as systemic shock, because this monoclonal antibody is a protein foreign to the human body. The administration to human bodies of rat monoclonal antibody against acetylcholine receptor, therefore, is not desirable.
In the method for producing the human monoclonal antibody against acetylcholine receptor by using transformed cell lines obtained by transforming lymphocytes collected from the thymus of a patient of myasthenia gravis with Epstein-Barr virus, the antibody-producing ability of the transformed cell lines cannot be rated as very high. Also, detailed information about the human monoclonal antibody obtained by this method is not available.
Regarding the method for producing a human monoclonal antibody against acetylcholine receptor by the use of a hybridoma obtained from peripheral mononuclear cells of a patient of myasthenia gravis and human myeloma cell line, the only information available is the fact that the human myeloma cell line used therein are of the non-secretor secretor type possessing resistance to 8-azaguanine and the fact that the human monoclonal antibody is equivalent to the autoantibody against acetylcholine receptor. It has been known to the art that generally in the production of a hybridoma by the use of human myeloma cell line, the process of production is deficient in fusing efficiency and cloning efficiency and the produced hybridoma is deficient in antibody-producing ability [Journal of Immunological Methods, Vol. 61, pages 17-32 (1983)]. Thus, the aforementioned method in which the hybridoma obtained by the use of human myeloma cell line is utilized can hardly be called advantageous.